Assessment of Protein Domain Classifications: SCOP, CATH, Dali and EVEREST

Background: SCOP is a manual classification of protein domain structures. CATH is a classification of protein domain structures created through a combination of manual and automatic methods. The Dali Domain Classification (henceforth Dali) is an automatically generated classification of protein domain structures. EVEREST is an automatically generated classification of protein domains that uses sequence information alone. We present a systematic comparison of the aforementioned systems. Methodology / Principal Findings: We focus on the proper classification of each domain, rather than on the exact determination of its boundaries. We show a tradeoff between the granularity of classification and the level of agreement among the classification systems the coarser the granularity, the lower the agreement. SCOP and CATH generally agree with each other at fine and medium granularity levels of their hierarchies, but disagree at coarser levels. The agreement among SCOP and CATH exceeds the quality of matching between Dali to either one of them at each given granularity level. Furthermore, nearly all Dali families are of fine granularity. Although EVEREST uses no structural information, it agrees with SCOP to the same degree as does Dali. EVEREST’s agreement with CATH even exceeds that of Dali. The granularity of EVEREST families is generally between SCOP family level and the CATH S level. Conclusions: The medium granularity levels form a twilight zone where SCOP and CATH agree, whereas the automatic methods do not match them. Beyond that twilight zone the disagreement between SCOP and CATH becomes so high that no global reference is available. We suggest that a reconsideration of the classifications at these levels is due. EVEREST, a sequence-only method performs as well or better than Dali, a structure-only method. All data files generated during this study are available at http://www.everest. cs.huji.ac.il/3d-assessment/.